Targeting Tertiary Lymphoid Structures in Chronic Inflammatory Disorders – ATILA

Tertiary lymphoid structures (TLS) are ectopic lymphoid tissues that drive immune responses at sites of chronic inflammation. They are of widespread interest in biology and medicine since their presence dramatically influences disease course in autoimmune disorders, infection, and cancer. However, due to their small size and their development in chronically altered tissues, TLS cannot be selectively targeted or detected by imaging.
The current project aims at developing new methods to map and eventually destroy the TLS in a non-invasive manner. To this aim, a new formulation of injectable superparamagnetic particles will be produced and targeted to the TLS. A set of innovations in contrast agent design and material chemistry will be developed to dramatically increase targeting efficiency compared to existing methods. By combining these innovations, intravenously injected superparamagnetic particles will accumulate in TLS in large numbers, thereby allowing their non-invasive detection by magnetic resonance imaging (MRI) and magnetic particle imaging (MPI). This will also open the possibility of thermal destruction of TLS using magnetic hyperthermia, providing a way to suppress a local immune response without affecting systemic immunity. Experimental models involving the formation of TLS will be performed in mice to demonstrate the applicability of the approach.
The biomedical innovations of the ATILA project will have clinically relevant applications, such as diagnosis of chronic inflammation, prediction of the response to immune checkpoint inhibitors in cancer and spatially selective suppression of immunity in autoimmune diseases.